2-101305708-T-G

Variant names:

• chr2-101305708-T-G
• rs6711606
• NM_173647.4:c.460+2421A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173647.4(RNF149):​c.460+2421A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 151,846 control chromosomes in the GnomAD database, including 56,700 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.86 (56700 hom., cov: 31)
• Consequence: RNF149 NM_173647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 20 publications found

Genes affected

RNF149 (HGNC:23137): (ring finger protein 149) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in ubiquitin-dependent protein catabolic process. Predicted to act upstream of or within cellular response to xenobiotic stimulus; negative regulation of MAPK cascade; and regulation of protein stability. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF149	NM_173647.4	c.460+2421A>C		intron_variant	Intron 1 of 6	ENST00000295317.4	NP_775918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF149	ENST00000295317.4	c.460+2421A>C		intron_variant	Intron 1 of 6	1	NM_173647.4	ENSP00000295317.3
RNF149	ENST00000424632.5	n.460+2421A>C		intron_variant	Intron 1 of 7	2		ENSP00000399090.1

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130481 AN: 151726 Hom.: 56651 Cov.: 31

Gnomad AFR AF: 0.965

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.869

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.845

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.860 AC: 130581 AN: 151846 Hom.: 56700 Cov.: 31 AF XY: 0.860 AC XY: 63825 AN XY: 74198

African (AFR) AF: 0.965 AC: 40034 AN: 41484

American (AMR) AF: 0.875 AC: 13347 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2433 AN: 3470

East Asian (EAS) AF: 0.861 AC: 4423 AN: 5140

South Asian (SAS) AF: 0.666 AC: 3204 AN: 4810

European-Finnish (FIN) AF: 0.888 AC: 9351 AN: 10530

Middle Eastern (MID) AF: 0.870 AC: 254 AN: 292

European-Non Finnish (NFE) AF: 0.812 AC: 55100 AN: 67846

Other (OTH) AF: 0.837 AC: 1762 AN: 2106

Alfa AF: 0.820 Hom.: 98249

Bravo AF: 0.866

Asia WGS AF: 0.760 AC: 2647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.7
DANN	Benign	0.20
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6711606; hg19: chr2-101922170;